1) Field of the Invention
This invention relates to antibodies, a production method of the antibodies, hybridoma strains which produce the antibodies, a production method of the hybridomas and antigen proteins recognized by the antibodies.
2) Background Art
In case of allergic disease such as the bronchial asthma or the allergic rhinitis, at first, the production of IgE specific to the antigen is induced. Various mediators such as histamine, eosinophil chemotactic factor in allergy (ECF-A), leukotrienes, platelet-activating factor (PAF) and thromboxane are produced and released from mast cells, basophils and the like, activated by the induced IgE. As the result, allergic diseases are induced.
Specifically, mast cells play an important role in tissues for the induction of allergic diseases by releasing these chemical mediators. The mast cells are recognized in the periphery of blood vessels of every tissue in the body. Especially, the cells densely distribute in the area beneath the epidermis, the respiratory airways, the gastrointestinal tract mucosa and the like These mast cells differ in the phenotypes depending on the tissues where they distribute. In mice, the mast cells are divided into two types, connective tissue-type mast cells and mucosal mast cells (MMC), depending on the existing area, the size, fc-malin sensitivity, the contained chemical mediator and the like. Though there is no distinct difference such as MMC and CTMC in human mast cells, they are differentiated into tryptase positive cell (MC-T) and both tryptase and chymase positive cells (MC-TC). MC-T distributes in the lung tissue and the gastrointestinal tract mucosa, while MC-TC distributes in the skin tissue.
Human mast cells, unlike cells of other leukocytes, leave bone marrow for peripheral environment as pluripotent stem cells, and may differentiate into MC-T or into MC-TC following adhesion to either lung or skin fibroblast. Studies on differentiation and proliferation of human mast cells were not advanced compared with those of mouse mast cells. The reason is that the culture method of human mast cells in vitro was not established. When human bone marrow cells were cultured in the presence of IL-3, the finally induced products were mainly basophils and mast cells could not obtained. In 1989, Furitsu et al. succeeded in culturing human mast cells by a coculture of cord blood mononuclear cells with mouse fibroblasts. Subsequently, a factor participating in differentiation and proliferation of mast cells was identified on fibroblasts (stem cell factor, called SCF hereinafter). After its cDNA was cloned, the culture of human mast cells from mononuclear cells in the bone marrow, peripheral blood or embrio liver became possible by using SCF.
In order to make clear the mechanism of allergic inflammation and to provide with an appropriate cure thereof, it is necessary to obtain these mast cells from differing tissues in pure state and to know their properties distinctly.
Heretofore, to obtain these mast cells, specific to tissues, mast cells have been isolated from each tissue by the enzymatic method. But according to the method, the quantity of isolated cells was limited, for it was technically difficult to purify only the mast cells specific to a tissue.
Nowadays, various differentiated cells are obtained in large quantities by cell culture, and cell surface antigens specific to cells are made clear. Therefore, technologies for purifying homogeneous cells by using antibodies against these antigens are now well established. But concerning to mast cells, especially to connective tissue type-mast cells (MT-TC) distributed in the skin, neither specific cell surface antigens nor antibodies which recognize the antigens is obtained.